Despite recent declines in both incidence and mortality, colorectal cancer (CRC) is the fourth most commonly diagnosed cancer and the second most common cause of cancer deaths in the United States. The present project aims to provide guidance on how to further reduce the burden of this disease, considering interventions based on primary prevention, screening, and treatment improvement. To this end, a wide range of issues is addressed in order to provide an overview of relative effects of alternative intervention policies. This study is a collaboration between Memorial Sloan-Kettering Cancer Center and Erasmus University (Erasmus MC) in Rotterdam. We use a population based microsimulation model (MISCAN-Colon) to assess the effect of individual interventions and combinations on the burden of CRC. MISCAN was originally developed by Erasmus MC to assess screening interventions and has been extended in our current project to incorporate changes in risk factors, chemoprevention and treatment efficacy. This model simulates the full dynamic US population which makes it particularly suitable for assessment of effects of interventions on a population level, including effects on CRC incidence and mortality, and also on quality of life, demands for medical capacity and economic burden over time. In order to make reliable projections for the future, it is necessary to understand to what extent the decline in CRC incidence and mortality is attributable to changes in exposures to "lifestyle" factors, changes in use of screening, changes in treatment, or combinations of these factors. Therefore, the specific aims are to use the MISCAN microsimulation model to 1.) Estimate the absolute and relative contribution of changing lifestyle factors, screening, and improved therapy on the observed trends in CRC incidence and mortality in the United States 1975-2002;and then to explore future scenarios to 2.) Evaluate the potential impact of current and newly developing technologies on lifestyle interventions, chemoprevention, screening, and treatment improvement on future trends in CRC incidence and mortality in the US and 3.) Translate the impact of implementation of interventions found to be effective in reducing incidence and mortality under Aim 2, into the burden of colorectal cancer also with respect to life years gained, quality of life, required medical capacity and economic burden. Aims 2 and 3 will also consider targeted intervention for individuals with increased risk due to familial predisposition. The results from these analyses can be used to inform decisions of directing medical and public health resources to the most effective interventions in the appropriate risk groups. We will collaborate with NCI and other CISNET investigators in conducting this work.